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The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

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Abstract

Realgar-Indigo naturalis formula (RIF) is a traditional Chinese medicine containing As4S4 and effective in treating acute promyelocytic leukemia (APL). The dose of RIF remains to be determined in pediatric patients. Comparison of plasma arsenic concentrations and toxicity between RIF and arsenic trioxide (ATO) treatment in APL may help to establish an appropriate therapeutic dose of RIF for children. From October 2018 to March 2020, 19 pediatric patients with APL treated with SCCLG-APL protocol were included, 9 in RIF group at 135 mg/kg/day orally three times daily, and 10 in ATO group at 0.16 mg/kg/day intravenously over 12 h daily. Peak and trough plasma arsenic concentrations were assayed at D1, 2, 7 and 14 of induction treatment. Urine arsenic excretions were assessed with spot urine samples and the measurements were adjusted using creatinine. Toxicities were compared between two groups. The plasma arsenic concentration reached steady state at D7 either in the RIF or ATO group, and the mean peak and trough concentrations were similar between two groups (P > 0.05), which were 0.54 μmol/L and 0.48 μmol/L in RIF group, and 0.63 μmol/L and 0.51 μmol/L in ATO group, respectively. Urine arsenic excretion rate was positively correlated with the concentration of plasma arsenic. The rates of treatment-related adverse events were similar in two groups. In conclusion, the dose of RIF at 135 mg/kg/day may be an appropriate therapeutic dose in children with APL. Urine arsenic level can be used as an indicator to estimate plasma arsenic concentration. Trial registration www.clinicaltrials.gov NCT02200978.

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Acknowledgements

We thank the patients and their families for th eir willingness to participate in this trial, and all participants and research staff of all centers within SCCLG.

Funding

The Science and Technology Planning Project of Guangdong Province, China (Grant/Award Number: 2014A020221008), the Science and Technology Planning Project of Guangzhou, China (Grant/Award Number: 20160402012) and the Scientific research project of Guangdong Provincial Bureau of Traditional Chinese Medicine, China (Grant/Award Number: 20201056).

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Author notes

  1. Liu-Hua Liao, Yi-Qiao Chen, and Dan-Ping Huang are co-first authors.

Authors and Affiliations

  1. Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Liu-Hua Liao, Dan-Ping Huang, Yu Li, Cong Liang, Jie-Si Luo, Li-Na Wang, Xue-Qun Luo, Yan-Lai Tang, Xiao-Li Zhang & Li-Bin Huang

  2. Department of Pediatrics, Huizhou Municipal Central Hospital, Huizhou, China

    Liu-Hua Liao

  3. Department of Pediatric Hematology, Fujian Medical University Union Hospital, Fuzhou, China

    Yi-Qiao Chen

  4. Department of Pediatrics, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, China

    Li-Na Wang

  5. Department of Children’s Medical Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

    Zhong-Lu Ye

  6. Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Li-Hua Yang

  7. Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, China

    Hui-Rong Mai

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  1. Liu-Hua Liao
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Correspondence to Yan-Lai Tang, Xiao-Li Zhang or Li-Bin Huang.

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Liao, LH., Chen, YQ., Huang, DP. et al. The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia. Cancer Chemother Pharmacol 90, 45–52 (2022). https://doi.org/10.1007/s00280-022-04449-9

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  • DOI: https://doi.org/10.1007/s00280-022-04449-9

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